Famotidine (N-(aminosulfonyl)-3-[(diamin omethylene)]-4-thiazolyl]methyl]thio]propani midamide), is known commercially as Pepcid.RTM.. Famotidine has the ability to inhibit gastric acid secretion through a histamine H.sub.2 -receptor. Histamine H.sub.2 -receptor blocking agents have the ability to inhibit the basic secretion of gastric acid and the gastric acid secretion induced by gastrin histamine, methacholine or food. Therefore, these compounds are useful in the treatment of gastric ulcer and duodenal ulcer caused by the hypersecretion of gastric acid.
A process for preparing famotidine, or guanidinothiazole compounds, and medical compositions containing such compounds are described in U.S. Pat. No. 4,283,408, issued Aug. 11, 1981 to Hirata et al., which is incorporated herein by reference.
Famotidine is currently sold in a concentrated form by Merck, Sharpe and Dohme for admixing with a suitable diluent for parenteral administration. To achieve a useful shelf life of the concentrated famotidine solution, which has a pH of 5.3, the solution must be stored at refrigerated temperatures. After mixing, by a pharmacist or other medical personnel, of a suitable aliquot of the concentrated famotidine with the diluent, the shelf life of the admixed solution is limited to not more than 14 days for sterility purposes as required by hospitals and other healthcare providers. Furthermore, the admixed solution must be refrigerated to achieve this shelf life.
The mixing step required by the current famotidine product, the refrigerated storage of the concentrate, as well as its limited shelf life after admixing present several disadvantages. During the preparation of the admixed solution, a possibility exists of dosage miscalculation, as well as contamination of the solution during the mixing step. The refrigeration storage of the admixed solution is an inconvenience and requires special handling. The reduced shelf life and admixing step leads to increased waste disposal as the components required to prepare the admixed solution, such as vials, needles and bags, as well as the unused portion of the concentrated solution, must be properly discarded. All of these disadvantages, including special handling and extra components, contribute to higher costs of the admixed solution. Finally, in cases where needles are used during the mixing step, there is an increased possibility of needle sticks to medical personnel.
The formulations of the present invention overcome the disadvantages of existing famotidine solutions as they are premixed and stable at room temperature, without the need for refrigeration, for long periods of time. In addition, the present formulation avoids any potential problems of contamination, needle sticks, increased waste, and dosage calculation errors as medical personnel can simply pull a prepared bag off the shelf for immediate use.